pharmacogenomic study of neoadjuvant eribulin for her2 non-overexpressing breast cancer

Conditions: Breast Cancer

Summary: this is a prospective, non-randomized, open-label, multicenter, single-arm exploratory pharmacogenomic study of single agent eribulin as neoadjuvant therapy in patients with operable stage iii her2 non-overexpressing breast cancer.


Eligibility criteria:
inclusion criteria: * written informed consent, specifically highlighting the molecular characterization of tumor and genomic samples * age ≥18 years * histologically confirmed invasive breast carcinoma, with all of the following characteristics: * primary tumor ≥2cm in largest diameter (ct1-3) * cn0-1 * no evidence of distant metastasis (m0) * breast cancer (bc) eligible for primary surgery * available pre-treatment core (tru-cut) biopsy or possibility of performing one * her2-negative bc (as per local assessment), defined as either of the following: * 0-1+ expression by ihc * 2+ expression by ihc and in situ hybridization (fish/cish) without her2 gene amplification (\<4 her2 gene copies per nucleus, or a fish ratio \[her2 gene copies to cr17 signals\] of \<1.8) * is situ hybridization (fish/cish) without her2 gene amplification, independently of ihc * known hormone receptor (er/pgr) status (as per local assessment) or the possibility of performing the tests * known percentage of hormone receptor (er/pgr) and ki67-positive tumor cells (as per local assessment), or possibility of performing the tests * in the case of a multifocal tumor, the largest lesion must be ≥2 cm and designated the "target" lesion for all subsequent tumor evaluations and her2-negative status must be documented in all the tumor foci * ecog performance status of 0 or 1 * laboratory values as follows: * absolute neutrophil count (anc) ≥1.5 x 109/l * platelets count ≥100 x 109/l * hemoglobin ≥9 g/dl * serum bilirubin ≤1.5 time the upper limit of normal (uln) * alanine aminotransferase and aspartate aminotransferase (ast) ≤2.5 x uln * alkaline phosphatase ≤2.5 x uln * serum creatinine ≤1.5 mg/dl or calculated creatinine clearance ≥60 ml/m * absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule * ability and willingness to comply with study visits, treatment, testing, and to comply with the protocol * availability of genomic dna (via whole blood) exclusion criteria: * any prior treatment for primary invasive bc * metastatic, locally advanced or inflammatory (i.e., stage iii-iv) bc * bilateral invasive bc * multicentric bc, defined as the presence of two or more foci of cancer in different quadrants of the same breast * pre-existing peripheral neuropathy of any grade * uncontrolled hypertension (systolic \>150 mmhg and/or diastolic \>100 mmhg) * clinically significant (i.e., active) cardiovascular disease * long qt syndrome * concomitant use of inhibitors of hepatic transport proteins such as organic anion-transporting proteins, p-glycoprotein, multidrug resistant proteins etc * major medical conditions that might affect study participation (e.g., uncontrolled seizure disorder, uncontrolled pulmonary, renal or hepatic dysfunction, or uncontrolled infection) * other primary malignant tumors within the previous 5 years, except for adequately controlled limited basal cell carcinoma of the skin or carcinoma in situ of the cervix * known human immunodeficiency virus(hiv) infection or other active or serious infection requiring iv antibiotics at randomization * pregnancy or breastfeeding women * women of childbearing potential(\<2 years after the last menstruation) not using effective, non-hormonal means of contraception during the study and for a period of 6 months following the last administration of study drug * administration of any live virus vaccine within 8 weeks preceding study entry * use of any investigational agent within 30 days of administration of the first dose of study drug or concurrent treatment on another clinical study * requirement for radiation therapy concurrent with study anticancer treatment * known hypersensitivity to any of the study drugs or excipients * inability or unwillingness to abide by the study protocol or cooperate fully with the investigator or designee

Keywords: breast cancer eribulin neoadjuvant pam50 triple-negative luminal a luminal b